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1.
BMC Infect Dis ; 22(1): 75, 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35062891

RESUMO

BACKGROUND: Bronchiectasis is a chronic lung condition frequently associated with nontuberculous mycobacteria pulmonary (NTM) disease. Persons with these conditions are at increased risk of mortality. Patient reported outcome (PRO) instruments and the 6-minute walk test (6MWT) have been shown to predict mortality for several lung conditions, but these measures have not been fully evaluated for bronchiectasis and NTM. METHODS: We conducted a retrospective cohort study among adult patients enrolled in a natural history study of bronchiectasis at the National Heart, Lung, and Blood Institute. Electronic medical records were queried for demographic, clinical, microbiologic, radiographic, and PRO instrument data: St. George's Respiratory Questionnaire (SGRQ), Medical Research Council Dyspnea Scale, and the Pulmonary Symptom Severity Score (PSSS). The study baseline date was defined as the patient's first visit after January 1st, 2015 with a SGRQ or 6MWT completed. Follow-up was defined as the interval between the study baseline visit and date of death or December 31st, 2019. Sex-stratified Cox proportional-hazards regression was conducted to identify predictors of mortality. Separate models were run for each PRO and 6MWT measure, controlling for age, body mass index (BMI), fibrocavitary disease status, and M. abscessus infection. RESULTS: In multivariable Cox proportional-hazards regression models, the PSSS-severity (aHR 1.29, 95% CI 1.04-1.59), the 6MWT total distance walked (aHR 0.938, 95% CI 0.896-0.981) and distance saturation product (aHR 0.930, 95% CI 0.887-0.974) independently predicted mortality. In addition, BMI was significantly predictive of mortality in all models. CONCLUSIONS: The 6MWT and a PRO instrument capturing symptom severity are independently predictive of mortality in our cohort of bronchiectasis patients.


Assuntos
Bronquiectasia , Micobactérias não Tuberculosas , Adulto , Estudos de Coortes , Humanos , Pulmão , Estudos Retrospectivos , Teste de Caminhada
2.
Dig Dis Sci ; 67(6): 2123-2133, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34043121

RESUMO

BACKGROUND: Lifestyle modification is currently the only treatment for nonalcoholic fatty liver disease (NAFLD). The most effective way to motivate behavior change in this population is not well understood. AIMS: The aims of this study were to characterize the association between patient disease knowledge, attitudes, and behaviors and to determine the impact of an educational intervention. METHODS: Adults with NAFLD had the following assessed before and after an educational intervention: (1) disease knowledge; (2) health-related quality of life (HRQOL); (3) physical activity; (4) diet; (5) stages of change; and (6) clinical variables. RESULTS: Median age of the cohort (N = 248) was 53.5, 46% were male, 85% were white, and median body mass index was 33.9. Forty-eight percentage had nonalcoholic steatohepatitis, and 28% had cirrhosis. The median correct knowledge score was 73.6%, median Chronic Liver Disease Questionnaire-NAFLD was 5.2/7, and diet score was 7/16 (higher indicating unhealthy diets). The cohort was sedentary at baseline, with 46% and 60% in active phases of change for nutrition and physical activity, respectively. Fifty-six (22%) had all three high-risk behaviors (sedentary, poor diet scores, low stage of change), which was independently associated with depression. The educational intervention improved diet scores, HRQOL, stages of change, and weight. CONCLUSIONS: Despite good disease knowledge, NAFLD participants were sedentary and 1/4 had high-risk lifestyle behaviors. An educational intervention had positive impacts on clinical outcomes, though effect size was small. Pairing educational interventions with targeted interventions to motivate behavior change can improve care for patients with NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Adulto , Dieta , Exercício Físico , Feminino , Humanos , Estilo de Vida , Masculino , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/terapia , Qualidade de Vida
3.
Therap Adv Gastroenterol ; 14: 17562848211042200, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34567270

RESUMO

INTRODUCTION: The optimal approach to screening and risk stratification for non-alcoholic fatty liver disease is challenging given disease burden and variable progression. The aim of this study was to assess primary care physician and referring physician practice patterns regarding non-alcoholic fatty liver disease. METHODS: An anonymous nationwide survey was administered to primary care physicians, endocrinologists, and cardiologists in a: (1) tertiary academic hospital, (2) community hospital, and (3) the American College of Physicians Insider Panel. Survey domains assessed non-alcoholic fatty liver disease knowledge, recommendations for screening, risk stratification, treatment, and referral patterns. RESULTS: A total of 440 providers completed the survey (35.2% completion rate; N = 82 academic hospital, N = 21 community hospital, N = 337 American College of Physicians). Half were male (51.7%), 78% from internal medicine, with 5% subspecialists. Providers were knowledgeable regarding prevalence and risk factors for non-alcoholic fatty liver disease. 58% would support screening for non-alcoholic fatty liver disease and used liver enzymes to do so. Only 22.5% used serum biomarkers and 23% used transient elastography for risk stratification. Primary reason for referral was advanced fibrosis/cirrhosis. 80% reported barriers to treating non-alcoholic fatty liver disease. There was no consistent diet recommended. CONCLUSION: In this nationwide survey, we demonstrated that while overall disease knowledge was good, there was an important disconnect between current guidelines and real-world clinical practice. There is also significant heterogeneity in practice patterns for first-line therapy of non-alcoholic fatty liver disease and the majority of provider's report barriers to treating non-alcoholic fatty liver disease. These findings highlight the potential role for reevaluating screening and risk stratification recommendations in primary care to better align with needs in that setting.

4.
Cureus ; 13(6): e15365, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34239796

RESUMO

During the COVID-19 pandemic, many patients are hospitalized, and those suffering from in-hospital cardiac arrest (IHCA) have been previously reported to have poor outcomes. This is a single-center, retrospective, observational study conducted at the Veterans Affairs Medical Center, Washington, DC, USA. The inclusion criteria were: patients admitted to the hospital with a diagnosis of COVID-19 who underwent cardiopulmonary resuscitation (CPR) for IHCA. Patients were labeled as COVID-19 positive based on a laboratory-confirmed positive polymerase chain reaction test. Patients with do-not-resuscitate (DNR) orders, those who were made comfort care, or enrolled in hospice were excluded. The study was approved by the hospital's institutional review board. A total of 155 patients with COVID-19 infection were admitted; 145/155 (93.5%) admitted to the medical floor and 10/155 (6.5%) to the medical intensive care unit (MICU). 36/145 (24.8%) floor patients were upgraded to MICU. Of the 46 patients treated in MICU, 17/46 (36.9%) were excluded for DNR status. From the remaining 29/46 (63.1%) patients, 19/29 (65.5%) patients survived, and 10/29 (34.5%) patients had IHCA. All 10/10 (100%) died after CPR without return of spontaneous circulation (ROSC). The initial rhythm was non-shockable in all patients, with pulseless electrical activity (PEA) in 7/10 (70%) and asystole in 3/10 (30%) patients. Patients with COVID-19 infection who had an IHCA and underwent CPR had a 0% survival at our hospital. Discussions on advanced care options, especially CPR, with COVID-19 patients and their families, are important as the overall prognosis after CPR for IHCA is poor.

5.
J Muscle Res Cell Motil ; 42(1): 59-65, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-31916128

RESUMO

Activity dependent potentiation is thought to result from phosphorylation of the regulatory light chains of myosin, increasing Ca2+ sensitivity. Yet, Ca2+ sensitivity decreases early in a period of intermittent contractions. The purpose of this study was to investigate the early change in Ca2+ sensitivity during intermittent submaximal tetanic contractions. Flexor digitorum brevis muscle fibres were dissected from mice after cervical disarticulation. Fibres were superfused with Tyrode solution at 32 °C. Length was set to yield maximal tetanic force. Indo-1 was microinjected into fibres and allowed to dissipate for 30 min. Fluorescence was measured at 405 and 495 nm wavelength and the ratio was used to estimate [Ca2+]. A control force-Ca2+ relationship was determined with stimulation over a range of frequencies, yielding constants for slope, max force, and half-maximal [Ca2+] (pCa2 +50). Data were collected for sequential contractions at 40 Hz at 2 s intervals. Active force decreased over the first 1-4 contractions then increased. A force-pCa2+ curve was fit to each contraction, using the control values for the Hill slope and max force by adjusting pCa2+50 until the curve passed through the target contraction. Data are presented for three contractions for each fibre: first, maximum shift to the right, and last contraction. There was a significant shift to the right for pCa2+50 (decreased Ca2+ sensitivity), usually early in the series of intermittent contractions, then pCa2 +50 shifted to the left, but remained significantly different from the control value. Although potentiation is associated with increased Ca2+ sensitivity, this increase begins only after Ca2+ sensitivity has decreased and, in most cases, Ca2+ sensitivity does not increase above the control level.


Assuntos
Cálcio/metabolismo , Contração Muscular/fisiologia , Animais , Feminino , Camundongos
6.
BMJ Case Rep ; 13(7)2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32723778

RESUMO

Emphysematous osteomyelitis (EO) is a rare infection associated with intraosseous gas. EO is an often fatal disease with an estimated 34% mortality. We present a case of a 63-year-old man with sternoclavicular EO with pleural involvement and significant subcutaneous emphysema diagnosed by CT. Extension of intraosseous gas into the pleural cavity is an extremely interesting presentation that has not been previously reported. The patient underwent a multidisciplinary treatment approach with surgical debridement and an extended antibiotic course. Intraoperative cultures of the pectoralis muscle and bone biopsy grew pan-sensitive Escherichia coli Prompt recognition and treatment are paramount to avoid a potentially fatal outcome. A review of the literature of the previous 46 cases of EO is presented for associated risk factors, the role of surgical management and antibiotic therapy.


Assuntos
Clavícula , Enfisema/etiologia , Infecções por Escherichia coli/diagnóstico , Osteomielite/etiologia , Doenças Pleurais/complicações , Doenças Raras/etiologia , Antibacterianos/uso terapêutico , Diagnóstico Diferencial , Enfisema/diagnóstico , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Osteomielite/diagnóstico , Doenças Pleurais/diagnóstico por imagem , Doenças Raras/diagnóstico , Articulação Esternoclavicular/microbiologia
7.
Transplantation ; 103(11): e345-e354, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31415032

RESUMO

BACKGROUND: The true incidence and unique risk factors for recurrent and de novo nonalcoholic fatty liver (NAFLD) and nonalcoholic steatohepatitis (NASH) post-liver transplant (LT) remain poorly characterized. We aimed to identify the incidence and risk factors for recurrent and de novo NAFLD/NASH post-LT. METHODS: MEDLINE via PubMed, Embase, Scopus, and CINAHL were searched for studies from 2000 to 2018. Risk of bias was adjudicated using the Newcastle-Ottawa Scale. RESULTS: Seventeen studies representing 2378 patients were included. All were retrospective analyses of patients with post-LT liver biopsies, with the exception of 2 studies that used imaging for outcome assessment. Seven studies evaluated occurrence of recurrent NAFLD/NASH, 3 evaluated de novo occurrence, and 7 evaluated both recurrent and de novo. In studies at generally high or moderate risk of bias, mean 1-, 3-, and ≥5-year incidence rates may be 59%, 57%, and 82% for recurrent NAFLD; 67%, 40%, and 78% for de novo NAFLD; 53%, 57.4%, and 38% for recurrent NASH; and 13%, 16%, and 17% for de novo NASH. Multivariate analysis demonstrated that post-LT body mass index (summarized odds ratio = 1.27) and hyperlipidemia were the most consistent predictors of outcomes. CONCLUSIONS: There is low confidence in the incidence of recurrent and de novo NAFLD and NASH after LT due to study heterogeneity. Recurrent and de novo NAFLD may occur in over half of recipients as soon as 1 year after LT. NASH recurs in most patients after LT, whereas de novo NASH occurs rarely. NAFLD/NASH after LT is associated with metabolic risk factors.


Assuntos
Doença Hepática Terminal/complicações , Fígado Gorduroso/complicações , Transplante de Fígado/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/complicações , Biópsia , Doença Hepática Terminal/epidemiologia , Doença Hepática Terminal/cirurgia , Fígado Gorduroso/diagnóstico , Fígado Gorduroso/epidemiologia , Humanos , Incidência , Análise Multivariada , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Período Pós-Operatório , Recidiva , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
8.
BMJ Case Rep ; 12(5)2019 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-31110070

RESUMO

A case report of spontaneous regression of pulmonary amyloidosis, diffuse interstitial pattern, in an elderly patient.


Assuntos
Amiloidose/patologia , Pneumopatias/patologia , Idoso de 80 Anos ou mais , Amiloidose/diagnóstico , Biópsia , Feminino , Humanos , Pneumopatias/diagnóstico , Linfonodos/patologia , Mediastinoscopia
9.
Fed Pract ; 36(2): 64-71, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30867626

RESUMO

Improvement in NAFLD may lead to improvement of metabolic syndrome, cardiovascular disease, and malignancy and vice versa.

10.
Dig Dis Sci ; 63(10): 2813-2814, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30043282

RESUMO

The original version of the article unfortunately contained errors in Table 3, Risk Factor column headings "Age > 50 (n = 115)," "Age > 50-64 (n = 154)," and "Age > 65 + (n = 60)."

11.
Hepatology ; 68(6): 2317-2324, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29729194

RESUMO

Access to specialty care has been associated with improved survival in patients with liver disease but universal access is not always feasible. Methods of care delivery using virtual modalities including the SCAN-ECHO (Specialty Access Network-Extension of Community Healthcare Outcome) program were implemented by the Veterans Health Administration (VHA) to address this need but limited data are available on patient outcomes. We sought to evaluate the efficacy of a SCAN-ECHO visit within the context of a regional cohort of patients with liver disease in the VHA (n = 62,237) following implementation in the Ann Arbor SCAN-ECHO Liver Clinic from June 1, 2011, to March 31, 2015. The effect of a SCAN-ECHO visit on all-cause mortality was compared with patients with no liver clinic visit. To adjust for the differences among patients who had a SCAN-ECHO visit versus those with no visit, propensity score matching was performed on condition factors that affect the likelihood of a SCAN-ECHO visit: demographics, geographic location, liver disease diagnosis, severity, and comorbidities. During the study period, 513 patients who had a liver SCAN-ECHO visit were found within the cohort. Patients who had completed a virtual SCAN-ECHO visit were more likely younger, rural, with more significant liver disease, and evidence for cirrhosis. Propensity-adjusted mortality rates using the Cox Proportional Hazard Model showed that a SCAN-ECHO visit was associated with a hazard ratio of 0.54 (95% confidence interval 0.36-0.81, P = 0.003) compared with no visit. Conclusion: Improved survival in patients using SCAN-ECHO suggests that this approach may be an effective method to improve access for selected patients with liver disease, particularly in rural and underserved populations where access to specialty care is limited.


Assuntos
Hepatopatias/mortalidade , Consulta Remota/estatística & dados numéricos , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , United States Department of Veterans Affairs
12.
Dig Dis Sci ; 63(9): 2259-2266, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29779083

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Severe NAFLD with advanced fibrosis results in substantial morbidity and mortality. Associated with metabolic syndrome, NAFLD is often initially clinically silent, yet intensive lifestyle intervention with 7% or greater weight loss can improve or resolve NAFLD. Using a Veterans Health Administration (VHA) liver biopsy cohort, we evaluated simple noninvasive fibrosis scoring systems to identify NAFLD with advanced fibrosis (or severe disease) to assist providers. METHODS: In our retrospective study of a national VHA sample of patients with biopsy-proven NAFLD or normal liver (2005-2015), we segregated patients by fibrosis stage (0-4). Non-NAFLD liver disease was excluded. We evaluated the diagnostic accuracy of the NAFLD fibrosis score (NFS), fibrosis-4 calculator (FIB-4), aspartate aminotransferase-to-alanine aminotransferase ratio (AST/ALT ratio), AST-to-platelet ratio index (APRI), and body mass index, AST/ALT ratio, and diabetes (BARD) score by age groups. RESULTS: We included 329 patients with well-defined liver histology (296 NAFLD and 33 normal controls without fibrosis), in which 92 (28%) had advanced (stage 3-4) fibrosis. Across all age groups, NFS and FIB-4 best predicted advanced fibrosis (NFS with 0.676 threshold: AUROC 0.71-0.76, LR + 2.30-22.05, OR 6.00-39.58; FIB-4 with 2.67 threshold: AUROC of 0.62-0.80, LR + 4.70-27.45, OR 16.34-59.65). CONCLUSIONS: While NFS and FIB-4 scores exhibit good diagnostic accuracy, FIB-4 is optimal in identifying NAFLD advanced fibrosis in the VHA. Easily implemented as a point-of-care clinical test, FIB-4 can be useful in directing patients that are most likely to have advanced fibrosis to GI/hepatology consultation and follow-up.


Assuntos
Técnicas de Apoio para a Decisão , Cirrose Hepática/diagnóstico , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , United States Department of Veterans Affairs , Saúde dos Veteranos , Adolescente , Adulto , Idoso , Alanina Transaminase/sangue , Área Sob a Curva , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Biópsia , Índice de Massa Corporal , Ensaios Enzimáticos Clínicos , Bases de Dados Factuais , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Feminino , Nível de Saúde , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/epidemiologia , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Contagem de Plaquetas , Testes Imediatos , Valor Preditivo dos Testes , Prevalência , Prognóstico , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Estados Unidos/epidemiologia , Adulto Jovem
13.
Pflugers Arch ; 470(8): 1243-1254, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29671103

RESUMO

Fatigue of single mouse fibers during repeated high-frequency stimulation results initially from decreased Ca2+ sensitivity while free myoplasmic calcium concentration ([Ca2+]m) increases, followed by decreasing [Ca2+]m. Recovery of active force with low-frequency stimulation is slow and persistent fatigue results from low [Ca2+]m. However, the consequences of intermittent submaximal contractions are not known. The aim of the present study was to investigate the changes in [Ca2+]m and active force during intermittent submaximal contractions and subsequent recovery. Single fibers of mouse flexor digitorum brevis muscles at 32 °C were stimulated with 40 or 50 Hz, for 350 ms every 2 s for 2 min and then every 1 s until < 40% of initial force. Values obtained during the intermittent stimulation were compared with a control force-[Ca2+]m relationship. A "P"-shaped pattern in the force-[Ca2+]m relationship was observed during intermittent stimulation. Early in the intermittent stimulation, [Ca2+]m increased while active force decreased. Subsequent force potentiation was accompanied by increased Ca2+ sensitivity. Later, as active force declined, [Ca2+]m decreased significantly (p < 0.001). This was followed, in the final phase, by a significant decrease in Ca2+ sensitivity determined by [Ca2+]m at half-maximal force (Ca50) (p = 0.001). Low-frequency fatigue persisted during recovery while Ca50 was not significantly different from prefatigue (p > 0.5). In conclusion, the main mechanism of fatigue is due to decreases in both [Ca2+]m and Ca2+ sensitivity following the initial force potentiation. The intermittent submaximal contractions resulted in persistent low-frequency fatigue seen during recovery, which was explained by depressed [Ca2+]m with no change in Ca2+ sensitivity.


Assuntos
Cálcio/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/fisiologia , Animais , Estimulação Elétrica/métodos , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Contração Muscular/fisiologia , Fadiga Muscular/fisiologia
15.
Dig Dis Sci ; 62(12): 3344-3349, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29043594

RESUMO

BACKGROUND AND AIMS: To improve subspecialty access, VA Ann Arbor Healthcare System (VAAAHS) implemented the first Specialty Care Access Network (SCAN)-Extension of Community Healthcare Outcomes (ECHO) in chronic liver disease. SCAN-ECHO Liver links primary care providers (PCPs) to hepatologists via secure video-teleconferencing. We aim to describe characteristics of participants (PCPs) and patients (clinical question and diagnosis) in SCAN-ECHO Liver. METHODS: This is a prospective study of the VAAAHS SCAN-ECHO Liver (June 10, 2011-March 31, 2015). This evaluation was carried out as a non-research activity under the guidance furnished by VHA Handbook 1058.05. It was approved through the Medicine Service at VAAAHS as noted in the attestation document which serves as documentation of approved non-research, quality improvement activities in VHA. RESULTS: In total, 106 PCPs from 23 sites participated. A total of 155 SCAN-ECHO sessions discussed 519 new and 49 return patients. 29.4% of Liver Clinic requests were completed in SCAN-ECHO Liver. SCAN-ECHO Liver consults were completed an average of 10 days sooner than in conventional clinic. Potential travel saving was 250 miles round-trip (median 255 (IQR 142-316) per patient. CONCLUSION: SCAN-ECHO Liver provided specialty care with increased efficiency and convenience for chronic liver disease patients. One of three of Liver Clinic consults was diverted to SCAN-ECHO Liver, reducing consult completion time by 20%.


Assuntos
Acessibilidade aos Serviços de Saúde , Hepatopatias/terapia , Encaminhamento e Consulta/organização & administração , Serviços de Saúde Comunitária , Humanos , Estudos Prospectivos
16.
PLoS Pathog ; 13(7): e1006515, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28753640

RESUMO

We have previously shown that the Mycobacterium tuberculosis universal stress protein Rv2623 regulates mycobacterial growth and may be required for the establishment of tuberculous persistence. Here, yeast two-hybrid and affinity chromatography experiments have demonstrated that Rv2623 interacts with one of the two forkhead-associated domains (FHA I) of Rv1747, a putative ATP-binding cassette transporter annotated to export lipooligosaccharides. FHA domains are signaling protein modules that mediate protein-protein interactions to modulate a wide variety of biological processes via binding to conserved phosphorylated threonine (pT)-containing oligopeptides of the interactors. Biochemical, immunochemical and mass spectrometric studies have shown that Rv2623 harbors pT and specifically identified threonine 237 as a phosphorylated residue. Relative to wild-type Rv2623 (Rv2623WT), a mutant protein in which T237 has been replaced with a non-phosphorylatable alanine (Rv2623T237A) exhibits decreased interaction with the Rv1747 FHA I domain and diminished growth-regulatory capacity. Interestingly, compared to WT bacilli, an M. tuberculosis Rv2623 null mutant (ΔRv2623) displays enhanced expression of phosphatidyl-myo-inositol mannosides (PIMs), while the ΔRv1747 mutant expresses decreased levels of PIMs. Animal studies have previously shown that ΔRv2623 is hypervirulent, while ΔRv1747 is growth-attenuated. Collectively, these data have provided evidence that Rv2623 interacts with Rv1747 to regulate mycobacterial growth; and this interaction is mediated via the recognition of the conserved Rv2623 pT237-containing FHA-binding motif by the Rv1747 FHA I domain. The divergent aberrant PIM profiles and the opposing in vivo growth phenotypes of ΔRv2623 and ΔRv1747, together with the annotated lipooligosaccharide exporter function of Rv1747, suggest that Rv2623 interacts with Rv1747 to modulate mycobacterial growth by negatively regulating the activity of Rv1747; and that Rv1747 might function as a transporter of PIMs. Because these glycolipids are major mycobacterial cell envelope components that can impact on the immune response, our findings raise the possibility that Rv2623 may regulate bacterial growth, virulence, and entry into persistence, at least in part, by modulating the levels of bacillary PIM expression, perhaps through negatively regulating the Rv1747-dependent export of the immunomodulatory PIMs to alter host-pathogen interaction, thereby influencing the fate of M. tuberculosis in vivo.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Transporte/metabolismo , Mycobacterium tuberculosis/metabolismo , Tuberculose/microbiologia , Transportadores de Cassetes de Ligação de ATP/química , Transportadores de Cassetes de Ligação de ATP/genética , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas de Transporte/química , Proteínas de Transporte/genética , Humanos , Mycobacterium tuberculosis/química , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/crescimento & desenvolvimento , Proteínas de Ligação a Fosfato , Fosforilação , Ligação Proteica , Domínios Proteicos , Técnicas do Sistema de Duplo-Híbrido
17.
Gastroenterol Clin North Am ; 45(2): 333-43, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27261902

RESUMO

Primary biliary cirrhosis (PBC) is a liver-specific autoimmune disease that primarily affects women (female-to-male ratio, 10:1) between 40 and 60 years of age. Metabolic bone disease is a common complication of PBC, affecting 14% to 52% of patients, depending on the duration and severity of liver disease. The osteoporosis seen in PBC seems mainly due to low bone formation, although increased bone resorption may contribute. Treatment of osteoporosis consists primarily of antiresorptive agents. Additional large prospective, long-term studies in patients with PBC are needed to determine efficacy in improving bone density as well as reducing fracture risk.


Assuntos
Reabsorção Óssea , Cirrose Hepática Biliar/complicações , Osteogênese , Osteomalacia/etiologia , Osteoporose/etiologia , Conservadores da Densidade Óssea/uso terapêutico , Doenças Ósseas Metabólicas/tratamento farmacológico , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/metabolismo , Cálcio da Dieta/uso terapêutico , Difosfonatos/uso terapêutico , Humanos , Cirrose Hepática Biliar/metabolismo , Osteomalacia/tratamento farmacológico , Osteomalacia/metabolismo , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Vitamina D/uso terapêutico
18.
Am J Gastroenterol ; 111(6): 838-44, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27021199

RESUMO

OBJECTIVES: Access to subspecialty care may be difficult for patients with liver disease, but it is unknown whether access influences outcomes among this population. Our objectives were to determine rates and predictors of access to ambulatory gastrointestinal (GI) subspecialty care for patients with liver disease and to determine whether access to subspecialty GI care is associated with better survival. METHODS: We studied 28,861 patients within the Veterans Administration VISN 11 Liver Disease cohort who had an ICD-9-CM diagnosis code for liver disease from 1 January 2000 through 30 May 2011. Access was defined as a completed outpatient clinic visit with a gastroenterologist or hepatologist at any time after diagnosis. Multivariable logistic regression was used to determine predictors of access to a GI subspecialist. Survival curves were compared between those who did and those who did not see a specialist, with propensity score adjustment to account for other covariates that may affect access. RESULTS: Overall, 10,710 patients (37%) had a completed GI visit. On multivariable regression, older patients (odds ratio (OR) 0.98, P<0.001), those with more comorbidities (OR 0.98, P=0.01), and those living farther from a tertiary-care center (OR 0.998/mi, P<0.001) were less likely to be seen in clinic. Patients who were more likely to be seen included those who had hepatitis C (OR 1.5, P<0.001) or cirrhosis (OR 3.5, P<0.001) diagnoses prior to their initial visit. Patients with an ambulatory GI visit at any time after diagnosis were less likely to die at 5 years when compared with propensity-score-matched controls (hazard ratio 0.81, P<0.001). CONCLUSIONS: Access to ambulatory GI care was associated with improved 5-year survival for patients with liver disease. Innovative care coordination techniques may prove beneficial in extending access to care to liver disease patients.


Assuntos
Assistência Ambulatorial , Acessibilidade aos Serviços de Saúde , Hepatopatias/terapia , Comorbidade , Feminino , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Especialização , Taxa de Sobrevida , Estados Unidos , Veteranos
20.
Dig Dis Sci ; 60(4): 1024-30, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25354830

RESUMO

BACKGROUND: Given the rising epidemics of obesity and metabolic syndrome, nonalcoholic steatohepatitis (NASH) is now the most common cause of liver disease in the developed world. Effective treatment for NASH, either to reverse or prevent the progression of hepatic fibrosis, is currently lacking. AIM: To define the predictors associated with improved hepatic fibrosis in NASH patients undergoing serial liver biopsies at prolonged biopsy interval. METHODS: This is a cohort study of 45 NASH patients undergoing serial liver biopsies for clinical monitoring in a tertiary care setting. Biopsies were scored using the NASH Clinical Research Network guidelines. Fibrosis regression was defined as improvement in fibrosis score ≥1 stage. Univariate analysis utilized Fisher's exact or Student's t test. Multivariate regression models determined independent predictors for regression of fibrosis. RESULTS: Forty-five NASH patients with biopsies collected at a mean interval of 4.6 years (±1.4) were included. The mean initial fibrosis stage was 1.96, two patients had cirrhosis and 12 patients (26.7 %) underwent bariatric surgery. There was a significantly higher rate of fibrosis regression among patients who lost ≥10 % total body weight (TBW) (63.2 vs. 9.1 %; p = 0.001) and who underwent bariatric surgery (47.4 vs. 4.5 %; p = 0.003). Factors such as age, gender, glucose intolerance, elevated ferritin, and A1AT heterozygosity did not influence fibrosis regression. On multivariate analysis, only weight loss of ≥10 % TBW predicted fibrosis regression [OR 8.14 (CI 1.08-61.17)]. CONCLUSION: Results indicate that regression of fibrosis in NASH is possible, even in advanced stages. Weight loss of ≥10 % TBW predicts fibrosis regression.


Assuntos
Dieta Redutora , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/dietoterapia , Redução de Peso , Adulto , Feminino , Fibrose , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/patologia , Estudos Retrospectivos
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